Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After the Same-Day, Varying Dosing Time Schedules of Eflapegrastim Administration in Patients With Breast-Cancer Receiving Docetaxel and Cyclophosphamide
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 50
- 试验地点
- 8
- 主要终点
- Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1
研究概览
简要总结
The purpose of this study is to compare the effect of Eflapegrastim on duration of neutropenia in patients with early-stage breast cancer when administered at varying intervals following Docetaxel and Cyclophosphamide administration.
详细描述
This is a Phase 1, randomized, open label, actively-controlled study to evaluate the same day dosing of Eflapegrastim on duration of neutropenia when administered at varying intervals following Docetaxel and Cyclophosphamide (TC) chemotherapy in patients with early-stage breast cancer.
The study will be conducted in two phases: Early Phase and Expansion Phase.
- In the Early Phase, approximately 45 patients were enrolled and randomized in a 1:1:1 ratio to 3 dosing time schedule arms. Each cycle was of 21 days. Total 4 cycles were evaluated for this phase. On Day 1 of Cycle 1, patients received Docetaxel and Cyclophosphamide (TC) chemotherapy followed by administration of Eflapegrastim at 1 of 3-time schedules post-TC (30 minutes [mins], 3 hours or 5 hours). During Cycles 2-4, patients received Eflapegrastim 24 hours after TC administration (on Day 2).
- In the Expansion Phase, additional 45 patients will be enrolled in Cycles 1-4, who will receive fixed dose of Eflapegrastim 30 mins after TC administration (on Day 1).
Safety evaluations will be conducted once the first 3 patients (for Early Phase) and the first 6 patients (for Expansion Phase) have completed Cycle 1 to determine if it is safe for patients to continue in that particular treatment arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and capable of giving written Informed Consent and able to adhere to study drug dosing time and blood draw schedules
- •New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
- •Candidate to receive adjuvant or neoadjuvant TC chemotherapy
- •Age must be at least 18 years for the Early Phase, and between 18 to ≤55 years for the Expansion Phase
- •ANC ≥1.5×10^9/liter (L).
- •Platelet count ≥100×10^9/liter (L).
- •Hemoglobin >10 grams per deciliter (g/dL).
- •Calculated creatinine clearance >50 milliliter per minute (mL/min).
- •Total bilirubin ≤1.5 milligrams per deciliter (mg/dL).
- •Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤2.5×upper limit of normal (ULN).
- •Alkaline phosphatase ≤2.0×ULN.
- •Eastern Cooperative Oncology Group (ECOG) ≤2
- •Willing to practice 2 forms of contraceptives (1 must be a barrier method), from study entry through 30 days after last dose of study drug/ early discontinuation
- •Negative urine pregnancy test within 30 days before randomization
排除标准
- •Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
- •Known sensitivity to Escherichia coli (E. coli) derived products
- •Concurrent adjuvant cancer therapy other than the trial-specified therapies
- •Locally recurrent/metastatic breast cancer
- •Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 3 months prior to the administration of study drug
- •Receiving anti-infectives, has an underlying medical condition or other serious illness that would impair the ability to receive protocol-specified treatment
- •Used any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study
- •Prior bone marrow or stem cell transplant
- •Prior radiation therapy within 30 days prior to enrollment
- •Major surgery within 30 days prior to enrollment
- •Pregnant or breastfeeding
研究组 & 干预措施
Early Phase: Eflapegrastim @ 30mins post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg granulocyte colony-stimulating factor [G-CSF]).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 30 minutes from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Eflapegrastim (Biological)
Early Phase: Eflapegrastim @ 30mins post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg granulocyte colony-stimulating factor [G-CSF]).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 30 minutes from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Docetaxel (Drug)
Early Phase: Eflapegrastim @ 30mins post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg granulocyte colony-stimulating factor [G-CSF]).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 30 minutes from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Cyclophosphamide (Drug)
Early Phase: Eflapegrastim @ 3 hours post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 3 hours from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Eflapegrastim (Biological)
Early Phase: Eflapegrastim @ 3 hours post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 3 hours from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Docetaxel (Drug)
Early Phase: Eflapegrastim @ 3 hours post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 3 hours from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Cyclophosphamide (Drug)
Early Phase: Eflapegrastim @ 5 hours post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 5 hours from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Eflapegrastim (Biological)
Early Phase: Eflapegrastim @ 5 hours post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 5 hours from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Docetaxel (Drug)
Early Phase: Eflapegrastim @ 5 hours post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycle 1: Administered on the same day as TC chemotherapy, 5 hours from the end of TC administration.
Cycles 2-4: Administered 24 hours after TC chemotherapy administration.
Each cycle is 21 days.
干预措施: Cyclophosphamide (Drug)
Expansion Phase: Eflapegrastim @ 30 mins post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycles 1-4: Administered on the same day as TC chemotherapy, 30 minutes following the end of TC administration.
Each cycle is 21 days.
干预措施: Eflapegrastim (Biological)
Expansion Phase: Eflapegrastim @ 30 mins post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycles 1-4: Administered on the same day as TC chemotherapy, 30 minutes following the end of TC administration.
Each cycle is 21 days.
干预措施: Docetaxel (Drug)
Expansion Phase: Eflapegrastim @ 30 mins post TC
Eflapegrastim (13.2 mg/0.6 mL fixed dose, equivalent to 3.6 mg G-CSF).
Supplied in prefilled single-use syringes for subcutaneous injection.
Cycles 1-4: Administered on the same day as TC chemotherapy, 30 minutes following the end of TC administration.
Each cycle is 21 days.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Time to Recovery of Absolute Neutrophil Count (ANC) From Nadir to ≥1.5×10^9/L in Cycle 1
时间窗: Cycle 1 is 21 days
Time to ANC Recovery is defined as the time from chemotherapy administration until the patient's ANC increases to ≥1.5×10\^9/liter (L) after the expected nadir.
次要结局
- Duration of Grade 4 Neutropenia (DSN) in Cycle 1(Cycle 1 is 21 days)
- Expansion Phase: Time to Recovery of ANC From Nadir to ≥1.5×10^9/L in Cycles 2-4(Cycles 2-4 (cycle length=21 days) (up to approximately 63 days))
- Expansion Phase: DSN in Cycles 2-4(Cycles 2-4 (cycle length=21 days) (up to approximately 63 days))
- Expansion Phase: Incidence of FN in Cycles 2-4(Cycles 2-4 (cycle length=21 days) (up to approximately 63 days))
- Expansion Phase: Proportion of Patients With Grade 4 Neutropenia in Cycles 2-4(Cycles 2-4 (cycle length=21 days) (up to approximately 63 days))
- Expansion Phase: Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycles 2-4(Cycles 2-4 (cycle length=21 days) (up to approximately 63 days))
- Number of Patients With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety(Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months))
- Proportion of Patients Discontinuing Because of a TEAE(Up to approximately 40 days after the last dose of study treatment or early study discontinuation (up to approximately 4 months))
- Incidence of Grade 3 Febrile Neutropenia (FN) in Cycle 1(Cycle 1 is 21 days)
- Incidence of Neutropenic Complications, Including Hospitalization due to Neutropenia, FN, and use of Anti-infectives During Cycle 1(Cycle 1 is 21 days)
- Proportion of Patients With Grade 4 Neutropenia in Cycle 1(Cycle 1 is 21 days)